Sickle cells target both tumor and vasculature

Usually associated with potentially life-threatening diseases, sickle cells may actually be helpful in the fight against cancer.

“Sickle cells appear to be a potent way to attack hypoxic, or oxygen-starved, solid tumors, which are notable for their resistance to existing cancer chemotherapy agents and radiation,” affirmed radiation oncologist Mark W. Dewhirst, DVM, PhD, director of the tumor microcirculation laboratory at Duke University Medical Center in Durham, North Carolina, in a statement issued by the medical center. Dewhirst is the senior author of the study yielding the sickle-cell findings (PLoS ONE. 2012;8[1]:e52543).

The genetic mutation that causes sickle cell anemia changes the shape of red blood cells into crescent moons, or sickles, making them less efficient at transporting oxygen through the body. Unlike healthy red blood cells that flow smoothly through vessels, sickle cells get stuck, causing painful and tissue-damaging blockages.

Dewhirst and colleagues infused fluorescently dyed sickle cells into mice with breast cancer and saw that within 5 minutes, the deformed cells began to adhere to blood vessels surrounding the hypoxic tumors. Over the course of 30 minutes, the sickle cells had formed clots and had begun blocking blood vessels feeding into the tumor.

According to Dewhirst, the hypoxic tumor produces an abundance of adhesion molecules as part of its distressed reaction to oxygen deprivation. The sickle cells snag onto those molecules. Once clustered within the tumor, sickle cells deposit a toxic iron residue as they die, causing tumor cells to die as well.

When the researchers added zinc protoporphyrin alone or in combination with doxorubicin to the sickle cells, even greater oxidative stress occurred in the tumor and surrounding blood vessels. This quadrupled the delay in tumor growth, compared with tumors exposed to regular blood cells. The mice showed no acute toxicity to the sickle cell treatment.

“In contrast to existing treatments directed only to the hypoxic tumor cell, the present approach targets the hypoxic tumor vascular environment and induces injury to both tumor microvessels and tumor cells,” summarized the investigators in their report. “Thus, the [sickled erythrocytes appear] to be a potent new tool for treatment of hypoxic solid tumors.”